Genome sequence of bacteriophage Janeemi isolated on Arthrobacter globiformis from soil collected in New York.

Janeemi is a bacteriophage that infects Arthrobacter globiformis B-2880, which was isolated from soil collected in New York City. The genome has a length of 43,877 bp and contains 69 predicted genes. Based on gene content similarity to phages in the actinobacteriophage database, Janeemi is assigned to phage cluster AZ1.

A mechanistic insight on how Compromised Hydrolysis of Triacylglycerol 7 (CHT7) restrains the involvement of it's CXC domain from quiescence repression.

CHT7 is a regulator of quiescence repression in Chlamydomonas reinhardtii. Initially, CHT7's repression activity was thought to be managed by its DNA-binding CXC domain. Later, it was found that the CHT7-CXC domain is dispensable for CHT7's activities. Rather, CHT7's predicted protein domains were proposed to be involved in regulation activities by binding to other repressors in the cell. Yet, it remains unclear why and how CHT7 refrains its CXC domain from participating in any transcriptional activities. The question becomes more intriguing, since CXC binding regions are available in promoter regions of some of the misregulated genes in CHT7 mutant (cht7). Through biophysical experiments and molecular dynamics approaches, we studied the DNA recognition behavior of CHT7-CXC. The results indicate that this domain possesses sequence selectivity due to the differential binding abilities of its subdomains. Further, to understand if the case is that CXC loses its DNA binding capabilities in the vicinity of other repressors, we examined CHT7-CXC's DNA binding stability under the spatial constraint conditions created through fusing CHT7-CXC with AsLOV2. The results show limited ability of CHT7-CXC to withstand steric forces and provide insights to why and how algal cells may hold back CHT7-CXC's indulgence in quiescence repression. CLASSIFICATIONS: Biological Sciences, Biophysics and Computational Biology.

Efficacy of Transarterial Chemoembolization Combined With Camrelizumab in the Treatment of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Hepatocellular carcinoma (HCC) is the most common primary cancer of liver tissue and is often caused by chronic liver diseases. The Barcelona Clinic Liver Cancer (BCLC) staging system is commonly used to determine the stage and prognosis of HCC. Transarterial chemoembolization (TACE) is the recommended first-line therapy for intermediate-stage HCC (patients who have asymptomatic, multi-nodular hepatocellular carcinoma). Over the past 10 years, the combination of TACE with immune checkpoint inhibitors, such as Camrelizumab, has shown promising results in treating HCC. We conducted a systematic review and meta-analysis following PRISMA guidelines. A comprehensive search of PubMed, MEDLINE, Elsevier, Scopus, ATC abstracts, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases was performed to identify relevant studies on the effectiveness of TACE combined with Camrelizumab in the treatment of HCC. Study selection, data extraction, and quality assurance were conducted by independent investigators. From 1023 identified citations, six studies were included in the final analysis. The combined results of these studies showed a complete response rate of 7.35%, a partial response rate of 37.10%, stable disease in 28.76% of patients, an objective response rate of 46.13%, a disease control rate of 77.19%, and progression-free survival of 6.2 months. The combination of TACE and Camrelizumab appears to be a safe and effective treatment option for patients with advanced, recurrent, and unresectable HCC. However, the included studies had limitations such as retrospective design and small sample sizes. Further research is needed to validate and expand on these findings.

Disruption of the FMN-A524 interaction cascade and Glu513-induced collapse of the hydrophobic barrier promotes light-induced Jα-helix unfolding in AsLOV2.

The C-terminal Jα-helix of the Avena sativa's Light Oxygen and Voltage (AsLOV2) protein, unfolds on exposure to blue light. This characteristic seeks relevance in applications related to engineering novel biological photoswitches. Using molecular dynamics simulations and the Markov state modeling (MSM) approach we provide the mechanism that explains the stepwise unfolding of the Jα-helix. The unfolding was resolved into seven steps represented by the structurally distinguishable states distributed over the initiation and the post initiation phases. Whereas, the initiation phase occurs due to the collapse of the interaction cascade FMN-Q513-N492-L480-W491-Q479-V520-A524, the onset of the post initiation phase is marked by breaking of the hydrophobic interactions between the Jα-helix and the Iß-strand. This study indicates that the displacement of N492 out of the FMN binding pocket, not necessarily requiring Q513, is essential for the initiation of the Jα-helix unfolding. Rather, the structural reorientation of Q513 activates the protein to cross the hydrophobic barrier and enter the post initiation phase. Similarly, the structural deviations in N482, rather than its integral role in unfolding, could enhance the unfolding rates. Furthermore, the MSM studies on the wild-type and the Q513 mutant, provide the spatiotemporal roadmap that lay out the possible pathways of structural transition between the dark and the light states of the protein. Overall, the study provides insights useful to enhance the performance of AsLOV2-based photoswitches.

Insights from the molecular docking analysis of gambogic acid with the Chikungunya spike glycoprotein E2.

Chikungunya fever is a mosquito-borne disease caused by the chikungunya virus (CHIKV) and has drawn substantial attention in recent years. So far, no effective treatment is available in the form of drugs or vaccines. In this study, we aimed to screen some drugs against the pathogenic Chikungunya virus through a molecular docking approach. As a fact, the spike E2 protein plays an important role in viral attachment to the human host cell, binding to a cell receptor MXRA8. The molecules screened for in-silico interaction against MXRA8 were selected with top hit based on binding affinity. The existing intermolecular bonds were investigated further in the active site of the protein that interacts with the top-hit ligands. Gambogic acid (guttic acid) was depicted as the furthermost potential inhibitor when compared to the others it had the lowest binding affinity (-10.9 kcal/mol). Gambogic acid, as a potential antiviral agent against the spike E2 protein, could be a promising candidate.

Draft Genome Sequences of Bacillus velezensis Strains AF_3B and OS2, Bacillus amyloliquefaciens Strain BS9, Bacillus halotolerans Strain A1, and Bacillus sp. Strain BS3, Producing Biosurfactants with Antimicrobial Potential.

Five environmental Bacillus strains were sequenced, of which three were isolated from the rhizosphere of agricultural soil and one each from Attock Oil Refinery and Khewra Salt Mine in Pakistan. The strains can be used for plant growth promotion and biosurfactant activity brought about by secondary metabolites.

Parkinson's Disease: A Current Perspectives on Parkinson's Disease and Key Bioactive Natural Compounds as Future Potential Drug Candidates.

Parkinson's disease (PD) is one of the most common types of neurological disorder prevailing worldwide and is rapidly increasing in the elderly population across the globe. The cause of PD is still unknown, but a number of genetic as well as environmental factors contributing to the pathogenesis of Parkinson's disease have been identified. The hallmark of PD includes dopamine deficiency (neurotransmitter imbalance) due to the gradual loss of dopaminergic nerves in the substantia nigra in the midbrain. Studying the mutation of associated genes is particularly informative in understanding the fundamental molecular and pathogenic changes in PD. Intracellular accumulation of misfolded or degraded protein due to mutated genes leading to the manifestation of mitochondrial dysfunction, oxidative stress followed by multifaceted patho-physiologic symptoms. Other studies include the appearance of both motor and non-motor responses like resting tremor, muscle stiffness, slow movement and anxiety, anaemia, constipation, rapid eye movement sleep behaviour disorder. Many bioactive natural compounds have shown positive pharmacological results in treating a number of extensive disease models of PD. Despite the availability of end number of potent medicinal plants around the world, limited research has been done associated with various neurological disorders, including PD. The currently available dopamine-based drug treatments have several side-effects, further, not effective enough to combat PD completely. Therefore, various plant-based compounds with medicinal benefits have grabbed lots of attention of researchers to deal with various life-threatening neurodegenerative disorders like PD. On the basis of literature available till date, here, we have discussed and addressed the molecular basis, current scenario, and the best possible treatment of PD for the future with minimal or no side-effects using various key bioactive compounds from natural origin/medicinal plants.

Comparison of exergaming and vestibular training on gaze stability, balance, and gait performance of older adults: A single blind randomized control trial.

Objectives: To compare the effects of exergaming and vestibular training on gaze stability, balance and gait performance of older adults. METHODS: The single-blind randomised controlled trial was conducted from August to October 2020 at the Doctor Raza Clinic, Swabi, Pakistan, and comprised individuals of both genders aged 60-75 years. The subjects were randomised into two groups using the sealed envelope method. Group 1 received exergaming, while group 2 received vestibular training 3 days a week for 6 weeks. The outcomes measures were dynamic gait index, time up and go test and non-instrumented dynamic visual acuity test. Data was analysed using SPSS 21. RESULTS: Of the 24 subjects, 12(50%) were in each of the two groups. Overall, there were 16(66%) males and 8(33%) females with a mean age of 66.3±4.36 years. Intra-group improvement was significant compared to the baseline (p<0.05) in both the differences, but inter-group differences across all parameters were non-significant (p>0.05). CONCLUSIONS: Both exergaming and vestibular training has similar effects on gaze stability, balance, and gait performance among the older adults. Clinical Trials.gov Identifier: NCT04414462.

Acclimation of cadmium-induced genotoxicity and oxidative stress in mung bean seedlings by priming effect of phytohormones and proline.

In this research, eight local mung bean (Vigna radiata) varieties were analyzed for their performance against two levels of CdCl2 solution (0.3 and 0.5 mM) alone and priming with gibberellic acid (GA3) (100 µM), salicylic acid (SA) (50 µM) and proline (5 mM) solution prior to Cd exposure. Mung bean seedlings were analyzed for disturbance in cytological, morphological, biochemical and enzymatic parameters under cadmium stress. For cytological studies, 48 h grown mung bean seedlings root tips were used to prepare slides and studied for percent mitotic index (MI%) and to calculate percent C-mitosis, laggard, sticky and fragmented chromosomes, pictures were captured by a Nikon camera (DS-Fi 1 Japan) attached with a microscope. One-week grown mung seedlings were studied for growth traits, malondialdehyde (MDA), protein, proline and antioxidant enzymes. ANOVA and DMR test of this research revealed that all the tested mung bean varieties and treatments were significantly different regarding mitotic index and number of chromosomal aberrations. Both the Cd treatments exhibited increased total chromosomal aberrations with different types and a maximum decrease in MI%. In pretreated samples, GA3, SA and proline serve as mitigating agents that reduce mutagenic effects of Cd in mung bean by increasing MI% and decreasing chromosomal aberrations as compared to non-pretreated samples. Both the Cd treatments showed a decrease in all growth traits. Total proteins were also found to be significantly reduced in a dose-dependent manner in all genotypes. Cd treatment increased the activities of all antioxidant enzymes tested. Cd caused oxidative damage as indicated by elevated levels of MDA content in treated samples in comparison to control. Proline content levels were also high in Cd treated seedlings indicating stress. Results demonstrated that pretreatment with phytohormones and proline before Cd were found to improve all morphological parameters, by altering antioxidant enzymes activities along with a decrease in MDA and proline contents as well. It was further noticed that the performance of GA3 was better at 0.3 mM Cd treatment while SA was found to be a good mitigating agent at 0.5 mM Cd stress in all tested mung bean varieties. This research concluded less deleterious effects of Cd on AZRI-2006 while more sensitivity to NM-51 towards Cd. Priming with phytohormones and proline is a user-friendly, economical, and simple mitigation strategy to reduce Cd toxicity in plants and get better yield from contaminated lands.

Clustering of countries for COVID-19 cases based on disease prevalence, health systems and environmental indicators.

The coronavirus has a high basic reproduction number ( R 0 ) and has caused the global COVID-19 pandemic. Governments are implementing lockdowns that are leading to economic fallout in many countries. Policy makers can take better decisions if provided with the indicators connected with the disease spread. This study is aimed to cluster the countries using social, economic, health and environmental related metrics affecting the disease spread so as to implement the policies to control the widespread of disease. Thus, countries with similar factors can take proactive steps to fight against the pandemic. The data is acquired for 79 countries and 18 different feature variables (the factors that are associated with COVID-19 spread) are selected. Pearson Product Moment Correlation Analysis is performed between all the feature variables with cumulative death cases and cumulative confirmed cases individually to get an insight of relation of these factors with the spread of COVID-19. Unsupervised k-means algorithm is used and the feature set includes economic, environmental indicators and disease prevalence along with COVID-19 variables. The learning model is able to group the countries into 4 clusters on the basis of relation with all 18 feature variables. We also present an analysis of correlation between the selected feature variables, and COVID-19 confirmed cases and deaths. Prevalence of underlying diseases shows strong correlation with COVID-19 whereas environmental health indicators are weakly correlated with COVID-19.

Multiple complications in sickle cell anaemia.

Sickle Cell Disease (SCD) is a structural haemoglobinopathy which is extremely diverse in its presentation regarding disease severity and organ involved. The homozygous form if poorly managed gives rise to numerous life threatening conditions which are otherwise avoidable. Here we report the case of a male adolescent with homozygous SCD who presented with haemolytic anaemia, massive ascites, hepatomegaly and multiple fractures secondary to severe malnourishment associated with the disease.

Frequency and Pattern of Bone Marrow Infiltration in Classical Hodgkin's Lymphoma: Experience from Southern Pakistan.

BACKGROUND: Hodgkin's lymphoma (formerly, Hodgkins disease) is a potentially curable malignancy with distinctive biological behavior and specific clinical characteristics. Limited information is available from developing countries for patients with classical Hodgkin's lymphoma (cHL). Therefore we reviewed the demographical and clinico-hematological profiles along with bone marrow infiltration patterns in adult patients presenting at Liaquat National Hospital and Medical College. MATERIALS AND METHODS: In this cross sectional study, 62 adult (≥15 years) patients with cHL were enrolled from January 2010 to December 2014. RESULTS: The mean age was 29.7±13.8 years with a median of 30 years. The male to female ratio was 2:1. B symptoms were present in 72.5% of patients and lymph node enlargement in 85.4%. The frequency of bone marrow infiltration in our cHL patients was found to be 27.4%, the pattern being predominantly focal followed by diffuse. The mean hemoglobin was 9.4±1.9g/dl with a mean MCV of 78.1±7.9 fl, a mean total leukocyte count of 10.9±20.6x109/l and a mean platelet count of 241.6±150.1x109/l. CONCLUSIONS: Our analysis shows that clinico-pathological features of cHL in Pakistan are comparable to published data. Peripheral lymphodenopathy associated with B symptoms is the commonest presentation. Bone marrow involvement is more common in our setup as patients usually presented at an advanced stage of disease.